Patients taking antipsychotic agents, especially clozapine, should be monitored regularly for hypertension and be initiated on antihypertensives (eg, angiotensin-converting enzymes [ACE] inhibitors, angiotensin receptor blockers [ARBs]) as indicated if hypertension develops. The findings comes from a new literature review published in the Journal of Clinical Pharmacy and Therapeutics.

Antipsychotics used to treat disorders such as schizophrenia, bipolar disorder, and other psychoses mainly involve D2 receptor antagonism (eg, phenothiazine, haloperidol) with some newer agents targeting D4 receptors (eg, clozapine, olanzapine). “[However] to our knowledge, systematic studies investigating the effect of selective dopamine receptor agonists and antagonists on blood pressure [BP] do not exist,” stated lead author NH Gonsai, PharmD candidate.

The researchers conducted a review to evaluate the association between dopamine antagonists with hypertension, with an emphasis on second-generation antipsychotic (eg, clozapine) use. They identified 11 human or animal studies, systematic reviews, meta-analyses, randomized controlled trials, and case report/series for inclusion in the analysis.

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The 5 dopamine receptor subtypes (eg, D1, D2, D3, D4, D5) play a role in sodium excretion and blood pressure. Specifically, the D1, D3, and D4 receptors interact with the renin-angiotensin-aldosterone system (RAAS) whereas the D2 and D5 receptors interact with the sympathetic nervous system for blood pressure regulation. Stimulating both D1 and D5 receptors directly has been shown to inhibit renal tubular sodium reabsorption.

The authors explained that dopamine agonists or antagonists could thus “disturb the regulation of BP by dopamine receptors.” Because of these associations, the authors recommend routine monitoring for hypertension for patients taking antipsychotic drugs. 

Future studies on concomitant antihypertensive agents with dopaminergic agonists or antagonists with strict blood pressure monitoring are needed to ultimately improve patient safety, the authors conclude.

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